H.G.M. Leufkens

Universiteit Utrecht, Utrecht, Utrecht, Netherlands

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Publications (331)590.79 Total impact

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    ABSTRACT: Risk Management Plans (RMPs) have become a cornerstone in pharmacovigilance of new drugs in Europe. The RMP was introduced in 2005 to support a proactive approach in gaining knowledge on safety concerns, through early planning of pharmacovigilance activities. The rate at which uncertainties in the safety profile are resolved through this proactive approach is, however, unknown. We therefore examined the evolution of safety concerns in the RMP after initial approval for a selected cohort of 48 drugs, to provide insight into the knowledge gain over time. We found that 20.7% of the uncertainties existing at approval had been resolved five years after approval. Since new uncertainties were included in the RMP at a similar rate, their overall number remained approximately equal. The relatively modest accrual of knowledge, as demonstrated in this study through resolution of uncertainties, suggests that opportunities for optimization exist while ensuring feasible and risk proportionate pharmacovigilance planning.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 15 September 2014. doi:10.1038/clpt.2014.184.
    Clinical pharmacology and therapeutics. 09/2014;
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    ABSTRACT: The risk of a subsequent major or any fracture after a hip fracture and secular trends herein were examined. Within 1 year, 2.7 and 8.4 % of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5 % after 5 years. Subsequent fracture rates increased during the study period both for major and any (non-hip) fracture.
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    ABSTRACT: Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe the time trends in antidepressant prescribing in the last decade and the variation in the prevalence, calculated in a uniform manner, in seven European electronic healthcare databases. Annual prevalence per 10,000 person-years (PYs) was calculated for 2001-2009 in databases from Spain, Germany, Denmark, the United Kingdom (UK), and the Netherlands. Prevalence data were stratified according to age, sex, antidepressant type (selective serotonin re-uptake inhibitors [SSRIs] or tricyclic antidepressants [TCAs]) and major indications. The age- and sex-standardized prevalence was lowest in the two Dutch (391 and 429 users per 10,000 PYs) and highest in the two UK (913 and 936 users per 10,000 PYs) populations in 2008. The prevalence in the Danish, German, and Spanish populations was 637, 618, and 644 users per 10,000 PY respectively. Antidepressants were prescribed most often in 20- to 60-year-olds in the two UK populations compared with the others. SSRIs were prescribed more often than TCAs in all except the German population. In the majority of countries we observed an increasing trend of antidepressant prescribing over time. Two different methods identifying recorded indications yielded different ranges of proportions of patients recorded with the specific indication (15-57 % and 39-69 % for depression respectively). Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations.
    European Journal of Clinical Pharmacology 05/2014; · 2.74 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate fracture risk in patients with Guillain-Barré syndrome (GBS). No association with risk of fracture was observed for GBS patients compared with controls. Only GBS patients using pain treatment had a doubled risk of fracture. Symptoms of Guillain-Barré syndrome (GBS) may vary from mild difficulty in walking to complete paralysis, which may increase the risk of fractures. Therefore, the aim of this study was to evaluate fracture risk in patients with GBS. We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (1987-2012). Each patient with GBS was matched by year of birth, sex, and practice, up to six patients without a history of GBS. Outcome measure was any fracture. There were no associations between GBS and any fracture, adjusted hazard ratio (AHR) 1.01 (95 % confidence interval [CI] 0.77-1.33), or osteoporotic fracture, AHR 0.76 (95 % CI 0.50-1.17), compared with controls. Stratification to gender, age, and duration since diagnosis did not show an association either. Only for GBS patients using pain treatment, risk of fracture was doubled AHR 1.97 (95 % confidence CI 1.21-3.21) compared with controls. The risk of fracture in GBS patients exposed to pain treatment was equivalent to risk of fracture among controls exposed to pain treatment. No association with risk of fracture was observed for GBS patients compared with controls. Only GBS patients using pain treatment had a doubled risk of fracture, but their risk was equivalent to fracture risk among controls exposed to pain treatment.
    Osteoporosis International 04/2014; · 4.04 Impact Factor
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    ABSTRACT: High cancer mortality rates in low- and middle-income countries (LMICs) have raised concerns regarding access to oncology medicines. Essential medicines are those which satisfy the primary health care needs and provide a basis for public procurement or reimbursement decisions in LMICs. We explored selection of oncology medicines in LMICs through investigating national essential medicines lists (NEMLs) for cancer treatments. Recently updated NEMLs were retrieved for 76 countries. Oncology medicines were classified based on therapeutic categories. Countries were clustered based on geographic regions, income levels and burden of cancer (mortality and morbidity). Indicators of frequency (number of medicines), diversity (number of therapeutic (sub)categories) and more importantly absence were measured and compared across countries using parametric and nonparametric tests. The overall median number of oncology medicines on NEMLs was 16 (interquartile range = 23) chosen predominantly from subcategories of 'antineoplastic agents', with substantial variation across regions and income groups. Five countries did not select any oncology medicine and 68% did not have any 'hormones and related agents' on their NEMLs. Newer technologies like targeted therapies were infrequently incorporated. The cluster of countries suffering most from the burden of cancer selected more essential oncology medicines and diversified further. The observed selection of oncology essential medicines can reflect insufficiencies and inequalities in access to cancer treatments at least in the public sector of LMICs. Further resources need to be allocated from governments and international organizations to tackle the problem of access to oncology medicines in these countries.
    Annals of Oncology 01/2014; 25(1):270-6. · 7.38 Impact Factor
  • European geriatric medicine 09/2013; 4:S178. · 0.63 Impact Factor
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    ABSTRACT: The aim of the study was to determine fracture risk in incident muscular dystrophy (MD) patients. Patients with MD are at a 1.4-fold increased risk of fracture as compared with population-based control patients. Risk further increased among elderly and female patients and among patients exposed to oral glucocorticoids. Muscular dystrophies (MDs) are inherited diseases causing muscle weakness and thereby increase the risk of falling and detrimental effects on bone. Both are recognised risk factors for fracture. Therefore, the aim of this study was to determine the hazard ratio of fracture in patients with MD. We conducted a retrospective cohort study using the UK General Practice Research Database (1987-2012). Each patient with MD was matched by year of birth, sex and practice to up to six patients without a history of MD. Outcome measure was all fractures. As compared with control patients, risk of any fracture was statistically significantly increased in MD patients (adjusted hazard ratio [AHR], 1.40; 95 % confidence interval [CI], 1.14-1.71). An increased risk of fracture was observed among MD patients with female gender (AHR, 1.78; 95 % CI, 1.33-2.40) and an increasing age as compared with control patients. Stratification to Duchenne MD showed no association with fracture, whereas risk of fracture was increased twofold among patients with myotonic dystrophy (AHR, 2.34; 95 % CI, 1.56-3.51). MD patients had an almost tripled risk of fracture when they used oral glucocorticoids in the previous 6 months as compared to non-users with MD. Patients with MD are at a 1.4-fold increased risk of fracture as compared with population-based control patients. Especially in older age groups and female gender, the fracture risk of MD versus non-MD patients is increased, whereas exposure to glucocorticoids further increased fracture risk among MD patients.
    Osteoporosis International 08/2013; · 4.04 Impact Factor
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    ABSTRACT: Marketing authorization application dossiers of 17 orphan drugs (ODs) and 51 non-ODs evaluated by the European Medicines Agency (EMA) in the period 2009-2010 were compared. We aimed to identify whether any differences existed between ODs and non-ODs in number and type of deficits brought forward during the EMA review, regarding the clinical development plan, clinical outcome and medical need and studied whether these deficits were similarly associated with marketing approval in the EU. In 71% of the ODs dossiers and 65% of the non-ODs dossiers marketing approval was granted. Differences in deficits were found, but similarities in the way ODs and non-ODs were reviewed and marketing approval decisions were taken, underline that regulatory standards are equally high.
    Drug discovery today 07/2013; · 6.63 Impact Factor
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    ABSTRACT: Background: Anticoagulation control is often summarised using the percentage of time spent in therapeutic range (TTR). This method does not describe the timing and severity of fluctuations in the International Normalised Ratio (INR). Objective: To evaluate whether the TTR method can be improved by considering the patterns of INR over time. Methods: The cohort included adults aged 40+ years with atrial fibrillation (AF) and laboratory records of INR as recorded in the UK Clinical Practice Research Datalink. Statistical clustering techniques based on simple INR measures were used to describe the patterns of INR. Nested case-control studies calculated the odds ratios (ORs) for the risk of stroke, bleeding and mortality with TTR and different INR patterns. It was also evaluated whether cluster analyses improved the prediction of outcomes over TTR. Results: 27,381 patients were studied with a mean age of 73. The OR for mortality was 3.76 (95% confidence interval [CI] 3.03-4.68) in patients with <30% TTR compared to patients with 100% TTR. INR patterns were found to be best described by six different clusters. The cluster with the most unstable pattern was associated with the largest risk of mortality (OR 10.7, 95% CI 8.27-13.85) and stroke (OR 3.42, 95% CI 2.08-5.63). INR measures that predicted death independent of TTR included absolute difference between two subsequent INR measurements and change relative to the mean over time. Conclusion: Cluster analysis of INR patterns improved prediction of clinical outcomes over TTR and may help to identify warfarin users who need additional anticoagulation monitoring. © 2012 International Society on Thrombosis and Haemostasis.
    Journal of Thrombosis and Haemostasis 10/2012; · 6.08 Impact Factor
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    ABSTRACT: With the European economy in the midst of the deepest recession since the 1930s and countries struggling to weigh up national and community interests, one may overlook accomplishments made in other areas of the European co-operation. Since the start of the European Union (EU) medicines approval system in 1995, the European regulatory environment has faced many challenges, but also made ample progress. Significant achievements are seen in unifying and improving regulatory practices, streamlining the way of bringing medicinal products to the clinic, thereby improving that new medicines become available to patients in the EU in an harmonized and evidence-based way.[1, 2] With the European Medicines Agency (EMA) coordinating a wide array of regulatory procedures, EU member states are contributing in many ways to the regulatory network, e.g. as rapporteur of individual dossiers, by work-sharing, guideline development, and cross learning. Recently, both the EMA and the Heads of Medicines Agencies (HMA) published their future strategy papers (i.e. European Medicines Agency Road Map to 2015: The Agency's contribution to Science, Medicines, Health and the HMA; A Strategy for the Heads of Medicines Agencies 2011-2015), aiming at strengthening the European regulatory network and its contribution to patients' access to medicinal products, public health and innovation.[3, 4].
    British Journal of Clinical Pharmacology 10/2012; · 3.69 Impact Factor
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    ABSTRACT: To examine the risk of fracture in patients with multiple sclerosis (MS) compared with population-based controls. A population-based cohort study was performed in the Dutch PHARMO Record Linkage System (1998-2008). Patients with MS (n = 2,415) were matched by year of birth, sex, and practice to up to 6 patients without MS (controls). We used Cox proportional hazards models to estimate the hazard ratio (HR) of fracture in MS. Time-dependent adjustments were made for age, history of disease, and drug use. During follow-up, there were 59 fractures among patients with MS (2.4%) and 227 fractures among controls (1.8%). Patients with MS had a 1.7-fold increased risk of osteoporotic fracture (HR 1.73 [95% confidence interval (CI) 1.18-2.53]) and a 4-fold increased risk of hip fracture (HR 4.08 [95% CI 2.21-7.56]). The risk of osteoporotic fracture was significantly greater for patients with MS who had been prescribed antidepressants (HR 3.25 [95% CI 1.77-5.97]) or hypnotics/anxiolytics (HR 3.40 [95% CI 2.06-5.63]) in the previous 6 months, compared with controls. Increased awareness of the risk of hip fracture is warranted in patients with MS, especially in those who have recently been prescribed antidepressants or hypnotics/anxiolytics.
    Neurology 05/2012; 78(24):1967-73. · 8.30 Impact Factor
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    ABSTRACT: This study was aimed at assessing the extent of safety learning from data pertaining to other drugs of the same class. We studied drug classes for which the first and second drugs were centrally registered in the European Union from 1995 to 2008. We assessed whether adverse drug reactions (ADRs) associated with one of the drugs also appeared in the Summary of Product Characteristics (SPC) of the other drug, either initially or during the postmarketing phase. We identified 977 ADRs from 19 drug pairs, of which 393 ADRs (40.2%) were listed in the SPCs of both drugs of a pair. Of these 393 that were present in both SPCs of a drug pair, 241 (61.3%) were present when the drug entered the market and 152 (30.7%) appeared in the postmarketing phase. The mention of ADRs in the SPCs of both same-class drugs in the postmarketing phase was associated with type A ADRs, marketing in the same regulator country, a longer time interval between entry into the market by the two drugs, and an earlier date of ADR. Although there appears to be some degree of safety learning from same-class drugs, there is still room for improvement, possibly by increasing proactive risk management.
    Clinical Pharmacology &#38 Therapeutics 03/2012; 91(5):872-80. · 6.85 Impact Factor
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    ABSTRACT:   Multiple sclerosis (MS) has been associated with increased mortality rates. However, influence of lifestyle parameters remains unknown, and inconsistencies exist regarding findings for causes of death.   We conducted a population-based cohort study using the General Practice Research Database, Hospital Episode Statistics, and national death certificates (January 2001 through March 2008). To each patient with MS (n = 1270), up to six referent subjects without MS were matched by age, gender, and practice. Cox proportional hazards models were used to estimate mortality rate ratios (HRs).   Patients with MS had a 3.5-fold increased mortality rate for all-cause mortality, compared with referent subjects (HR 3.51, 95% CI 2.63-4.69). The rate further increased amongst current smokers (HR 6.72, 95% CI 4.16-10.87) (but not in ex-smokers) and subjects with a body mass index of <20 kg/m(2) (HR 6.67, 95% CI 3.50-12.73). The HR was highest for infectious/respiratory-related deaths (HR 7.69, 95% CI 4.92-12.02) and was significantly increased for deaths related to cardiovascular diseases (2.4-fold) and cancer (1.9-fold), but not for accidents and suicide related deaths.   British patients with MS have a 3.5-fold increased mortality rate compared with the general population. Smoking and respiratory diseases are major (potentially preventable) factors related to increased mortality rate amongst patients with MS.
    European Journal of Neurology 02/2012; 19(7):1007-14. · 4.16 Impact Factor
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    ABSTRACT: Achtergrond: Veel mensen met angst- of slaapstoornissen krijgen van hun dokter een benzodiazepine voorgeschreven. Langdurig gebruik zorgt echter voor gewenningsproblemen en hoge maatschappelijke kosten. Om deze effecten te beperken heeft het ministerie van VWS de vergoeding van benzodiazepinen per 1 januari 2009 uit de basisverzekering gehaald. Sindsdien betalen de meeste gebruikers de kosten van benzodiazepinen zelf. Methode: In de gegevens van het Landelijk Informatie Netwerk Huisartsenzorg (LINH) keken wij hoeveel mensen tussen januari 2007 en december 2009 voor het eerst de diagnose slaap- en angststoornissen kregen bij de huisarts. Daarna onderzochten wij hoeveel recepten voor een benzodiazepine deze patiënten kregen en hoeveel van hen er ook weer mee stopten, en zo ja wanneer. Ook keken wij naar het aantal recepten voor een selectieve serotonineheropnameremmer (SSRI). Resultaten: Van de 13.596 patiënten die aan de voorwaarden voldeden had iets meer dan de helft een angststoornis, de anderen hadden een slaapprobleem. In 2009 kregen minder mensen de diagnose slaap- of angststoornis te horen dan in 2008. Ook het benzodiazepinegebruik daalde. Van de patiënten met slaapstoornissen kreeg 67,0% in 2008 een benzodiazepine voorgeschreven, versus 59,1% in 2009, en voor angststoornissen waren deze percentages 33,7% in 2008 versus 30,1% in 2009. Ook het aantal mensen dat meer dan één recept kreeg, daalde: voor slaapproblemen van 42,6% naar 35,0%, voor angststoornissen van 42,6% naar 36,4%. Slechts een klein (maar toenemend) aantal angstpatiënten stapte over op een SSRI: 0,3% in 2009 tegenover 0,1% in 2008. Conclusie: Het reduceren van de vergoeding heeft geleid tot een lichte daling in het aantal diagnoses, voorschriften en vervolgrecepten. Deze daling was groter bij slaapproblemen dan bij angststoornissen. De uitkomsten ondersteunen het beleid van de regering en laten zien dat er ruimte bestaat om het gebruik van deze geneesmiddelen te reduceren. (aut.ref.)
    Huisarts en wetenschap 01/2012;
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    ABSTRACT: This study aimed to provide an up-to-date description as well as comparative analysis of the national characteristics of pharmaceutical external price referencing (EPR) in Europe. Review of the country-specific PPRI (Pharmaceutical Pricing and Reimbursement Information) Pharma Profiles written by representatives of the PPRI Network. The Profiles were analysed according to predefined criteria. Of 28 analysed European countries 24 applied EPR in 2010. The majority of countries have statutory rules to implement EPR. Most countries had less than 10 countries in their reference baskets. Higher income countries tend to include higher income countries in their basket, whereas lower income countries refer to lower income countries. Taking the average price of all countries in the basket as the basis to calculate the national price was the most common strategy (n=8). The methodology of EPR has changed in most European countries over the past 10 years (n=19). EPR is a widely used pricing policy in Europe and is still actively used as well as adjusted by national authorities. However, we still see room for improvement by implementing more detailed legislations in terms of the revision of prices and by identifying alternative countries in case a product is not on the market. We also see the need for formal information sharing (e.g. congresses dedicated to pricing strategies and systems) with other public pricing authorities to learn about the different EPR methodologies as well as the national experiences. These congresses might also give room to better understand national pricing methods including discussions on possible limitations of these pricing methods.
    Health Policy 01/2012; 104(1):50-60. · 1.51 Impact Factor
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    ABSTRACT: Statins offer significant cardiovascular benefits. Their use, however, influences immune regulation, which may potentially facilitate autoimmunity, eventually resulting in autoimmune diseases such as rheumatoid arthritis (RA).The authors studied whether statin use was associated with an increased risk of developing RA by conducting a case-control study using the Netherlands Information Network of General Practice database. The authors identified 508 patients aged 40 years or older with a first-time diagnosis of RA in the period 2001-2006. Each RA case was matched to five controls for age, sex and index date, which was selected 1 year before the first diagnosis of RA. Odds ratios for the first-time diagnosis of RA were verified by a referral to a rheumatologist and/or at least one prescription of disease-modifying anti-rheumatic drugs and/or two prescriptions of corticosteroids after the date of first diagnosis. Cases were more often users of statins (15.9%) compared to controls (8.6%). After adjustment for cardiovascular risk factors and use of comedication, statin use was associated with an increased risk of incident RA (adjusted OR, 1.71 (95% CI 1.16 to 2.53); p=0.007). A consistent trend of increasing risk with increased cumulative duration, cumulative defined daily doses and number of prescriptions was not observed. However, a small trend between the potency of statin treatment and the risk of RA was found. Statin use seems to be associated with an increased risk of developing RA. Our findings should be replicated by additional studies.
    Annals of the rheumatic diseases 10/2011; 71(5):648-54. · 8.11 Impact Factor
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    ABSTRACT: Type 2 diabetes has been associated with an increased risk of cancer. This study examines the effect of more vs less intensive glucose control on the risk of cancer in patients with type 2 diabetes. All 11,140 participants from the Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial (ClinicalTrials.gov NCT00145925) were studied. Cancer incidence and cancer mortality was compared in groups randomised to intensive or standard glucose control. Information on events during follow-up was obtained from serious adverse event reports and death certificates. HRs (95% CI) were calculated for all cancers, all solid cancers, cancer deaths and site-specific cancers. After a median follow-up of 5 years, 363 and 337 cancer events were reported in the intensive and standard control groups, respectively (incidence 1.39/100 person-years [PY] and 1.28/100 PY; HR 1.08 [95% CI 0.93-1.26]). The incidences of all solid cancers and cancer deaths were 1.25/100 PY and 0.15/100 PY in the intensive group and 1.15/100 PY and 0.13/100 PY in the standard group (HR 1.09 [95% CI 0.93-1.27] for solid cancers, and 1.17 [0.75-1.84] for cancer death). Across all the major organ systems studied, no significant differences in the cancer incidences were observed in the intensive and standard control groups. More intensive glucose control achieved with a regimen that included greater use of gliclazide, insulin, metformin and other agents, did not affect the risk of cancer events or death in patients with type 2 diabetes.
    Diabetologia 07/2011; 54(7):1608-14. · 6.49 Impact Factor
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    F de Vries, T-P van Staa, H G M Leufkens
    Osteoporosis International 05/2011; 22(5):1641-2. · 4.04 Impact Factor
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    ABSTRACT: To investigate the main aims of the post-approval randomized controlled trials (RCTs) on etanercept and the extent to which they were designed to gain more comparative information. A search of the literature (Medline, Embase), trial registries (Clinical Trials.gov, Controlled Trials.com), and market authorization reports from the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) was carried out to identify all RCTs. A comparison of trial data identified unpublished trials and multiple publications relating to the same study. All RCTs completed and/or published after initial market approval was regarded as post-approval. Up until 2008, we found 84 post-approval trials, 11 (13%) trials on approved extensions of indication, another 30 (36%) trials on the approved indications, and 43 (51%) trials on indications not (yet) approved. Nearly half of the studies on indications not yet approved were initiated and funded by independent sponsors. After the initial approval of etanercept, six head-to-head trials were conducted on the approved indications. Overall, the main objectives of post-approval trials with etanercept were found to confirm efficacy and safety in new indications, and to gather additional information for optimal use on the approved indications. Post-approval RCTs on etanercept focus more on studies searching for new indications than on deepening knowledge about use. Ten years after the market entry of etanercept, one of the reasonable demands of clinical practice, for more comparative information, still remains unanswered.
    Scandinavian journal of rheumatology 05/2011; 40(3):183-91. · 2.51 Impact Factor
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    ABSTRACT: Recent initiation of proton-pump inhibitor (PPI) treatment may increase the risk of community-acquired pneumonia (CAP), hypothetically by allowing colonisation of the oropharynx by gastrointestinal bacteria. The aim of this study was to assess the causal pathway by considering microbial aetiology of pneumonia and indications for initiation of PPI treatment. This was a population-based, case-control study with 430 cases with pneumonia and 1,720 matched controls. An elaborate diagnostic protocol was used to identify the causative microorganism of pneumonia. For patients recently starting PPI treatment, indications for treatment were assessed. Recent initiation of PPI treatment (<30 days) was associated with an increased risk of CAP (adjusted OR 3.1, 95% CI 1.4-7.1). Oropharyngeal bacteria were evenly distributed among current users, past users and nonusers of PPIs (p=0.41). Gastrointestinal bacteria were identified in only five (1.2%) patients with pneumonia (two current users and three nonusers). Excluding patients who were possibly prescribed PPI treatment for early symptoms of pneumonia (protopathic bias) did not alter the study findings. This study reaffirmed that use of PPIs is associated with an increased risk of CAP, especially when treatment has recently been started. Neither protopathic bias nor shifts in microbial aetiology seem to explain the association.
    European Respiratory Journal 04/2011; 38(5):1165-72. · 6.36 Impact Factor

Publication Stats

3k Citations
590.79 Total Impact Points


  • 1993–2014
    • Universiteit Utrecht
      • • Division of Pharmacoepidemiology and Pharmacotherapy
      • • Utrecht Institute for Pharmaceutical Sciences
      Utrecht, Utrecht, Netherlands
  • 2002–2012
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands
    • University Medical Center Utrecht
      • Julius Center for Health Sciences and Primary Care
      Utrecht, Provincie Utrecht, Netherlands
  • 2008
    • Medicines and Healthcare products Regulatory Agency (MHRA)
      Londinium, England, United Kingdom
  • 2002–2007
    • TweeSteden Ziekenhuis
      Tilburg, North Brabant, Netherlands
  • 2002–2006
    • University of Southampton
      • MRC Lifecourse Epidemiology Unit
      Southampton, England, United Kingdom
  • 2005
    • University of Nottingham
      • School of Community Health Sciences
      Nottingham, ENG, United Kingdom
  • 2004
    • SWOV Institute for Road Safety Research
      Leyden, South Holland, Netherlands
  • 2003
    • Pharmo Institute for Drug Outcomes Research
      Utrecht, Utrecht, Netherlands
    • Altrecht GGZ
      Utrecht, Utrecht, Netherlands
  • 1999
    • Maastricht University
      • Department of Epidemiology
      Maestricht, Limburg, Netherlands
  • 1997
    • University Hospital Brussels
      Bruxelles, Brussels Capital Region, Belgium
  • 1995
    • Erasmus Universiteit Rotterdam
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands